Brain Death - Diagnosis

Instrumental methods confirming the diagnosis of brain death

There are many problems in diagnosing clinical criteria for brain death. Often, their interpretation is insufficient to diagnose this condition with 100% accuracy. In this regard, already in the first descriptions, brain death was confirmed by the cessation of bioelectrical activity of the brain using EEG. Various methods that allow confirming the diagnosis of "brain death" have received recognition throughout the world. The need for their use is recognized by most researchers and clinicians. The only objections concern the diagnosis of "brain death" based only on the results of paraclinical studies without taking into account the data of a clinical examination. In most countries, they are used when it is difficult to conduct a clinical diagnosis and when it is necessary to reduce the observation time in patients with a clinical picture of brain death.

It is obvious that the methods used to confirm brain death must meet certain requirements: they must be performed directly at the patient's bedside, they must not take much time, they must be safe for both the patient and the potential recipient of donor organs, as well as for the medical personnel performing them, they must be as sensitive, specific and protected from external factors as possible. The proposed instrumental methods for diagnosing brain death can be divided into 3 types.

• Direct methods confirming the cessation of biological activity of neurons: EEG, study of multimodal evoked potentials.
• Indirect methods used to confirm the cessation of intracranial blood flow and cerebrospinal fluid pulsation include: cerebral panangiography, transcranial dopplerography, echoes, cerebral scintigraphy with sodium pertechnetate labeled with ^99m Tc, subtraction intravenous angiography, magnetic resonance angiography (MR angiography), and spiral CT.
• Indirect methods that allow us to detect metabolic disorders in the dead brain include: determination of oxygen tension in the bulb of the jugular vein, infrared cerebral oximetry. Telethermography can also be attributed to them, since the temperature of various parts of the body reflects the level of metabolism of the underlying organs and tissues. Attempts to use such modern methods of determining the level of cerebral energy metabolism as PET, diffusion- and perfusion-weighted MRI programs are also described.

Electroencephalography

EEG was the first method used to confirm the diagnosis of "brain death". The phenomenon of bioelectrical silence of the brain was unambiguously assessed as a sign of the death of all neurons in the brain. Many studies have been conducted to determine the sensitivity and specificity of the method. A general review analysis conducted in 1990 showed that both the sensitivity and specificity of the method were within 85%. Such relatively low figures are due to the low noise immunity of EEG, which is especially evident in the conditions of the intensive care unit, where the patient is literally entangled in wires from the measuring equipment. The specificity of EEG reduces the phenomenon of suppression of bioelectrical activity of the brain in response to intoxication and hypothermia. Despite this, EEG remains one of the main confirmatory tests, it is widely used in many countries. Since many different methods of recording the bioelectrical activity of the brain have been described, the staff of the American Electroencephalographic Society have developed recommendations that include minimum technical standards for recording EEG necessary to confirm the bioelectrical silence of the brain. These parameters are prescribed by law in many countries and include the following formulations.

• The absence of electrical activity of the brain is established in accordance with international guidelines for EEG research in conditions of brain death.
• Electrical silence of the brain is taken as an EEG recording in which the amplitude of activity from peak to peak does not exceed 2 μV, when recording from scalp electrodes with a distance between them of at least 10 cm and with a resistance of up to 10 kOhm, but not less than 100 Ohm. Needle electrodes are used, at least 8, located according to the "10-20" system, and two ear electrodes.
• It is necessary to determine the integrity of the commutations and the absence of unintentional or intentional electrode artifacts.
• The recording is carried out on the channels of the encephalograph with a time constant of at least 0.3 s with a sensitivity of no more than 2 μV/mm (the upper limit of the frequency passband is not lower than 30 Hz). Devices with at least 8 channels are used. EEG is recorded with bi- and monopolar leads. Electrical silence of the cerebral cortex under these conditions should be maintained for at least 30 minutes of continuous recording.
• If there are doubts about the electrical silence of the brain, repeated EEG recording and assessment of EEG reactivity to light, loud sound and pain are necessary: the total time of stimulation with light flashes, sound stimuli and pain stimuli is not less than 10 min. The source of flashes, given at a frequency of 1 to 30 Hz, should be located at a distance of 20 cm from the eyes. The intensity of sound stimuli (clicks) is 100 dB. The speaker is located near the patient's ear. Stimuli of maximum intensity are generated by standard photo- and phonostimulators. Strong pricks of the skin with a needle are used for pain stimuli.
• An EEG recorded over the telephone cannot be used to determine electrical silence of the brain.

Thus, the widespread use of EEG is facilitated by the wide availability of both the recording devices themselves and specialists who are proficient in the technique. It should also be noted that EEG is relatively standardized. However, such disadvantages as low sensitivity to drug intoxication and poor noise immunity encourage the additional use of more convenient and sensitive techniques.

Study of multimodal evoked potentials

Various components of the curve during registration of acoustic brainstem evoked potentials are generated by the corresponding parts of the auditory pathway. Wave I is generated by the peripheral part of the auditory analyzer, wave II - in the proximal parts of the VIII cranial nerve, in the area of transition of n.acusticus from the internal auditory canal to the subarachnoid space, III-V components are generated by the brainstem and cortical parts of the auditory pathway. The results of numerous studies indicate that mandatory registration of the loss of waves III through V is necessary to confirm brain death. According to various authors, components I-II are also absent during the initial registration in 26-50% of patients whose condition meets the criteria for brain death. However, in the rest, these components are detected despite the cessation of intracranial blood flow for several hours. Several explanations for this phenomenon have been proposed, the most convincing of which seems to be the following assumption: since the pressure inside the labyrinth is somewhat lower than the intracranial pressure, residual perfusion is preserved in the labyrinthine artery basin after the onset of brain death. This is also confirmed by the fact that the venous outflow from the cochlea is protected from increased intracranial pressure by the surrounding bone structures. Thus, to diagnose brain death, it is necessary to register the absence of III-V waves of the curve. At the same time, it is necessary to register I or 1st waves as evidence of the integrity of the peripheral section of the auditory analyzer, especially if the patient has a craniocerebral injury.

Recording of SSEP allows to evaluate the functional state of both the brainstem and the cerebral hemispheres. Currently, SSEP is recorded in response to stimulation of the median nerve. Evoked responses can be recorded over all areas of ascending afferentation. In case of brain death, the cortical components of the curve will not be recorded, while the waves N13a and P13/14 recorded over the spinous process of the C _II vertebra are visible in most cases. If the lesion extends caudally, the last wave recorded will be N13a over the C _VII vertebra. Extensive mechanical bilateral damage to the hemispheres or brainstem can cause ambiguous interpretation of the results of recording SSEP. In this case, the pattern of loss of cortical response is identical to that in case of brain death. Of great interest is the work of Japanese authors who isolated the wave N18 recorded using a nasogastric electrode. According to their data, the disappearance of this component of SSEP indicates the death of the medulla oblongata. In the future, after conducting appropriate large prospective studies, this particular version of SSEP recording may replace the apneic oxygenation test.

The visual pathway does not pass through the brainstem, so VEPs reflect only the pathology of the cerebral hemispheres. In brain death, VEPs indicate the absence of a cortical response with possible preservation of the early negative component N50, which corresponds to the preserved electroretinogram. Therefore, the VEP method has no independent diagnostic value and, in terms of the range of application, approximately corresponds to conventional EEG, with the only difference being that it is more labor-intensive and difficult to interpret.

Thus, each type of evoked potentials has different information content in the diagnosis of brain death. The most sensitive and specific method is the acoustic brainstem evoked potentials. Next in line are SSEPs, and the rating is closed by VEPs. A number of authors propose to use a complex consisting of acoustic brainstem, somatosensory and VEPs to improve information content, using the term "multimodal evoked potentials" to designate this complex. Despite the fact that to date no large multicenter studies have been conducted to determine the information content of multimodal evoked potentials, such studies are included as confirmatory tests in the legislation of many European countries.

In addition, it is worth noting the attempts to use the study of the blink reflex state using electrical stimulation to confirm brain death. The blink reflex is identical to the corneal reflex, traditionally used in the diagnosis of the level and depth of damage to the brainstem. Its arc closes through the bottom of the fourth ventricle, accordingly, when the neurons of the brainstem die, the blink reflex disappears along with other brainstem reflexes. The equipment that supplies an electrical impulse to obtain the blink reflex is included in the standard composition of the device for recording multimodal evoked potentials, so isolated recording of the blink reflex has not become widespread.

In addition, the method of galvanic vestibular stimulation is of particular interest. It consists of bilateral stimulation of the mastoid process area with a direct current of 1 to 3 mA and a duration of up to 30 s. The direct current irritates the peripheral section of the vestibular analyzer, causing nystagmus, similar in its mechanism of development to caloric. Thus, the method of galvanic vestibular stimulation can be an alternative to conducting a caloric test for injuries of the external auditory canal.

Indirect methods for diagnosing brain death

The main stage of thanatogenesis of brain death is the cessation of cerebral blood flow. Therefore, instrumental research data confirming its absence for more than 30 minutes can absolutely accurately indicate brain death.

One of the first methods proposed to establish the cessation of intracranial blood flow was cerebral angiography. According to the recommendations, the contrast should be injected into each examined vessel under double pressure. The sign of cessation of blood circulation is the absence of contrast inflow into the cranial cavity, or the "stop phenomenon", observed in the internal carotid artery above the bifurcation of the common carotid artery, less often - at the entrance to the pyramid of the temporal bone or in the siphon area and in segments V ₂ or V ₃ of the vertebral arteries. This phenomenon should be observed in all 4 vessels feeding the brain: the internal carotid and vertebral arteries. Special multicenter standardized studies that would accurately determine the sensitivity and specificity of cerebral panangiography have not been conducted to date. Despite this, cerebral panangiography is included as one of the confirmatory tests in most clinical recommendations, mainly as an alternative to a long-term observation period. In our opinion, the aggressive and bloody method of cerebral panangiography, which is not indifferent even for a “planned” patient, is unacceptable in a situation with a severe patient with coma III for the following reasons.

• It is difficult to obtain the consent of a neuroradiologist to perform cerebral panangiography on such a seriously ill patient.
• The procedure of moving a patient in critical condition to the angiography room is incredibly complex. This requires the participation of at least 3 employees: a resuscitator, who provides manual assistance with artificial ventilation; a paramedic, who controls the IV with medications; an orderly, who moves the patient's bed.
• One of the most critical moments is transferring the patient to the angiographic table: in 3 out of 9 of our own observations, cardiac arrest occurred, which necessitated defibrillation.
• Not only patients are exposed to the danger of radiation, but also resuscitators, who are forced to continuously perform mechanical ventilation manually.
• The need to administer contrast under excessively high pressure due to severe cerebral edema-tamponade in patients with grade III-IV cerebral coma increases spasmogenicity, as a result of which so-called false carotid pseudo-occlusion may develop.
• A significant disadvantage of cerebral panangiography compared to ultrasound methods, telethermography and EEG is that it is a one-time study, in which the angiologist receives information about the blood circulation inside the skull within a few seconds. At the same time, it is known how different and variable the cerebral blood flow of a dying patient is. Therefore, it is ultrasound monitoring, and not a short-term idea of the passage or stoppage of contrast, that is the most informative method for diagnosing brain death.
• The economic costs are significantly higher with cerebral panangiography.
• Conducting aggressive cerebral panangiography on a dying patient contradicts the basic principle of healing: “Noli nосеrе!”
• Cases of false negative results in trepanned patients have been described.

Thus, cerebral panangiography, despite its high accuracy, cannot be considered an ideal method for confirming brain death.

Radionuclide diagnostic methods, in particular scintigraphy with ^99m Tc or single-photon emission CT with the same isotope, are used in many countries as a test confirming the diagnosis of "brain death". The failure of the isotope to enter the cranial cavity with the blood flow, called the "empty skull" phenomenon, almost completely correlates with the "stop phenomenon" observed during cerebral panangiography. Separately, it is worth noting an important symptom of brain death - the "hot nose" sign , which occurs due to the discharge of blood from the internal carotid artery system into the external branches that feed the facial part of the skull. This sign, pathognomonic of brain death, was first described in 1970, and has subsequently been repeatedly confirmed in numerous reports. A mobile gamma camera is usually used for scintigraphy, allowing this study to be carried out at the patient's bedside.

Thus, ^99m Tc scintigraphy and its modifications are highly accurate, quickly feasible and relatively safe methods of express diagnostics. However, they have one significant drawback - the impossibility of actually assessing the blood flow in the vertebrobasilar system, which is very important in the presence of only supratentorial lesions. In Europe and the USA, scintigraphy is included in clinical recommendations along with such methods confirming the cessation of intracranial blood flow as cerebral panangiography and TCDG (see Chapter 11 "Ultrasound Dopplerography and Duplex Scanning").

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